D2 and D1 dopaminergic activity of 7-OH-DPAT.

The D1 and D2 dopamine receptor agonist properties of 7-hydroxy-2-(N,N-di-n-propylamino) tetraline (7-OH-DPAT) was determined by investigating the effect of this compound on rat striatal acetylcholine (ACh) concentration and increase in cAMP formation in primary cerebellar granule cell cultures. 7-OH-DPAT at low doses (0.01 to 0.1 mumol/ kg) had no significant effect, and at high doses (0.3 to 30 mumol/kg) significantly (P < 0.01) increased striatal ACh levels. Likewise, quinpirole was found to significantly elevate ACh content. Pretreatment with haloperidol, a non-selective antagonist of the D2 family of receptors, significantly (P < 0.01) blocked 7-OH-DPAT- and quinpirole-induced increases in ACh. U-99194A, a D3 selective dopamine antagonist, had no significant effect on 7-OH-DPAT-induced increases in striatal ACh. However, raclopride, a D2 selective dopamine antagonist, completely blocked 7-OH-DPAT-induced elevations in ACh. 7-OH-DPAT in the mumolar range increased cAMP formation in granule cell cultures, and this effect was antagonized by SCH 23390, a D1 selective dopamine antagonist. The neurochemical study indicates that, at high doses, 7-OH-DPAT has both D1 and D2 agonist activities.